BACKGROUND: Meta-analysis had shown a significant 5% absolute survival benefit in favour of neoadjuvant chemotherapy (NAC) with cisplatin-based chemotherapy before radical cystectomy (RC) and pelvic lymphadenectomy (PLND) for patients with muscle invasive bladder cancer (MIBC). Those who had pathological complete response (pCR) to NAC could have long-term progression-free survival (PFS) and overall survival (OS). AIM: To identify the treatment and patient factors which could predict a pCR to NAC and the associated PFS and OS in a single institute. METHODS AND RESULTS: We retrospectively reviewed the records of patients who had received NAC with gemcitabine and cisplatin (GC) in our centre from January 2004 to December 2017. The patients' age, tumour stage, baseline estimated glomerular filtration rate (eGFR), chemotherapy chart, and pathological information were recorded. There were 25 men and five women who had received NAC followed by RC. pCR was noted in the surgical specimen of 11 (37%) patients. The mean dose of gemcitabine was significantly higher in the pCR group than the non-pCR group (9850 vs 7852 mg, P = 0.039) as was the dose-intensity of cisplatin (87.4% vs 71.3%, P = 0.044). After a median follow-up of 38 months (range 4.3-154), seven patients had disease progression. The estimated 3-year PFS is 74.9% (95% confidence interval [CI], 66.7%-83.3%). None of the patients who achieved pCR relapsed, while six out of seven patients who had pN1 disease developed distant metastasis (DM). Only two patients died of DM while two other patients died of unrelated causes. The estimated 3-year OS is 88.9% (95% CI 82.8%-95%). CONCLUSIONS: We have demonstrated that the dose intensity of GC is a major determinant of pCR, which predicts longer RFS and OS. Further research in gene expression profiling of MIBC to help selecting patient for NAC is needed.
BACKGROUND: Meta-analysis had shown a significant 5% absolute survival benefit in favour of neoadjuvant chemotherapy (NAC) with cisplatin-based chemotherapy before radical cystectomy (RC) and pelvic lymphadenectomy (PLND) for patients with muscle invasive bladder cancer (MIBC). Those who had pathological complete response (pCR) to NAC could have long-term progression-free survival (PFS) and overall survival (OS). AIM: To identify the treatment and patient factors which could predict a pCR to NAC and the associated PFS and OS in a single institute. METHODS AND RESULTS: We retrospectively reviewed the records of patients who had received NAC with gemcitabine and cisplatin (GC) in our centre from January 2004 to December 2017. The patients' age, tumour stage, baseline estimated glomerular filtration rate (eGFR), chemotherapy chart, and pathological information were recorded. There were 25 men and five women who had received NAC followed by RC. pCR was noted in the surgical specimen of 11 (37%) patients. The mean dose of gemcitabine was significantly higher in the pCR group than the non-pCR group (9850 vs 7852 mg, P = 0.039) as was the dose-intensity of cisplatin (87.4% vs 71.3%, P = 0.044). After a median follow-up of 38 months (range 4.3-154), seven patients had disease progression. The estimated 3-year PFS is 74.9% (95% confidence interval [CI], 66.7%-83.3%). None of the patients who achieved pCR relapsed, while six out of seven patients who had pN1 disease developed distant metastasis (DM). Only two patients died of DM while two other patients died of unrelated causes. The estimated 3-year OS is 88.9% (95% CI 82.8%-95%). CONCLUSIONS: We have demonstrated that the dose intensity of GC is a major determinant of pCR, which predicts longer RFS and OS. Further research in gene expression profiling of MIBC to help selecting patient for NAC is needed.
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Authors: Andrea Necchi; Andrea Anichini; Daniele Raggi; Alberto Briganti; Simona Massa; Roberta Lucianò; Maurizio Colecchia; Patrizia Giannatempo; Roberta Mortarini; Marco Bianchi; Elena Farè; Francesco Monopoli; Renzo Colombo; Andrea Gallina; Andrea Salonia; Antonella Messina; Siraj M Ali; Russell Madison; Jeffrey S Ross; Jon H Chung; Roberto Salvioni; Luigi Mariani; Francesco Montorsi Journal: J Clin Oncol Date: 2018-10-20 Impact factor: 44.544